JPH07100186A - Rapidly decomposable sheet-form dosage product and its production - Google Patents

Abstract

PURPOSE: To manufacture a sheet-like administration form of a drug, a sweetener, other food, or a cosmetic. CONSTITUTION: An oral administration/intake form has a film-like shape for various administratios. The form is constituted of a mixture of at least one kind of a film forming agent of 20-60 wt.%, at least one kind of a gel forming agent of 2-40 wt.%, at least one kind of active material of 0.1-35 wt.%, and an inactive filling agent below 40 wt.%. The form is fitted to a carrier, or it is used with no carrier while containing the above composition. In manufacturing, a polar solvent below 30 wt.% is added to the dense mixture of the components as required, and they are processed into a spreadable or extrudable material.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a sheet-shaped dosage form for oral administration or uptake of pharmaceuticals, confectionery, other foods, cosmetics and the like, and a method for producing the same.

[0002]

BACKGROUND OF THE INVENTION Pharmaceutical dosage forms of medicinal products, confectionery and other foodstuffs, as well as cosmetics to be applied to the oral area or in principle to be orally administered, are in principle free to administer by the person who administers or by the manufacturer. It is possible to be already pre-divided into dispensing units.

Such dispensed forms are especially common in the pharmaceutical industry in the form of tablets, capsules, coated tablets, pills, lozenges and the like.

Compared to drop solutions, ointments or creams which have to be dispensed by the user, in these cases an unintended undesired dispensing by the user is prevented.

From an application point of view, tablets have a certain minimum size (diameter 5 to 6 mm) and a certain minimum weight (about 10) to facilitate the handling of these dosage forms.
Must be 0 to 200 mg). Therefore, especially effective drugs are about 99% of the weight of tablets.
May contain inactive ingredients of.

[0006] Foods, especially confectioneries, are also often found on the market in individually formulated forms (candies, sweetener tablets, peppermint tablets, etc.). Here again-for example in the case of candy-there is the desire to achieve the desired taste by using a small amount of auxiliary agent (usually sugar).

For this reason, numerous technical proposals have recently been made, which aim to ensure the safe handling of these substances as well as the reduction of the amount of inactive ingredients in the product. .

Proposals of particular interest in this context are, for example, DE 3534983, DE 2746414,
BE637363, DE2432825, or D
The production of a sheet-shaped active substance carrier as described in the respective publications of E3630303.

According to known production methods, paper-like carriers of this type are first produced without active substance and then spray-coated with an active substance-containing solution (eg GB 1061).
557), and coating / printing with a high-concentration active substance-containing layer (eg, EP0219762).

However, conventional spraying or molding (eg JP 69026674) and drying followed by complete or incomplete dissolution of the active or inactive substance in water or other solvent (DE 242986).
No. 5) can be expected to be the method of choice of those skilled in the art.

Extrusion under heating has also been proposed {Reserch Disc Closure, 1986, No. 26
March, March, 145 to 146 (No. 26341)}.

Film-like formations promise the possibility of enormous variation in the separation of individual doses. These can be envisioned as having the shape of a stamp sheet that can be partially withdrawn from the complete composite in a very short time before use (eg BE637363, EP.
No. 0219762).

Individual doses of different size can also be promised from the tape-shaped dosage form, for example separated by perforation (eg DE 27464).
14 publication). It is absolutely necessary, in particular when using non-edible carriers, that complete separation into individual parts is necessary, but this requires a more hygienic, easy and safe separation.

Although a number of flat-shaped dosing regimens and methods are known to the person skilled in the art, the physics of pharmaceutical carriers such as, for example, the selection of adjuvants, and of sheet carriers of this type. There are still considerable deficiencies in the concept of chemical microstructure. Numerous purposes and aims must be taken into account.

Rapid disintegration is required for a large number of pharmaceuticals to allow rapid swallowing of the pharmaceutical dosage unit, while in other circumstances the pharmaceuticals may be temporarily edible. Adhesion to mucous membranes is required, and in other cases, for example short-acting pharmaceuticals, degradation with considerable delay is desired. In the case of confectionery, intermediate maintenance of, for example, flavor in the mouth is usually preferred.

The cosmetic film dentifrice should be flexible and disintegrate as soon as possible.

In general, the dosage form in sheet form must not be too brittle so that it can be safely transferred from its part to the destination. If a carrier is used, both materials must be properly fitted and adherent to each other for two reasons, one of which is the separation of the medication, for example by partial punching of the isolation insert and peel-off. Must be ensured during manufacture, and secondly, adhesion to the carrier must be effective during storage.

When drying is required during manufacture, it should be possible to make a spreadable formulation with as little solvent (preferably water) as possible and use as little energy as possible during the drying process. is there.

The pharmaceutical compositions known to date do not meet these requirements. The basic principle of tablet technology is described in DE 2746414 in the context of film tapes, which involves the use of thermoplastic binders or other auxiliaries as desired, chemical cross-linking, Or the addition of hydrophobic substances to delay degradation,
The combination of a few layers and the use of microencapsulated active substances.

Known tablet disintegrants use therein a disintegration aid for the film. According to the findings of the inventors themselves, these proposals cannot be applied to new medicinal products.

The conventional decomposing agent is a porous, mechanically stable environment formed by the adhesive force between particles, assuming that the decomposition is caused by swelling due to addition of water or accumulated elastic deformation energy. Need a situation.

However, these prerequisites do not always exist in the case of sheet-like dosage forms which are always slightly flexible and have low porosity. The swellable particles may delay the degradation of the film by removing water.

According to DE 2432925, the formulation contains a water-soluble cellulose ether, a separating agent and, if desired, a filler. Originally, however, most water-soluble polymers always required the addition of large amounts of water to make the material of sufficiently low viscosity for spreads or moulds, but this structure requires high drying costs during manufacture. Will be included.

In addition to this, the adhesive bond to the base is affected by the extreme shrinkage of this type of material.

When a dosage form in sheet form is made by spreading a water-based substance on a dehesive paper or film, the liquid easily runs off the support due to surface tension. Or at least form areas of different film thickness. Even if the viscosity is increased by adding a cellulose derivative or the like, it becomes more difficult to spread through a minute gap.

According to other sources (eg DE 3534981, DE 3630603), viscosity-forming substances are therefore recommended, although these give rise to low viscosity solutions by heat (in the coating machine), but Immediately after that, a gel-like stable film is formed by cooling,
Dry completely in air (eg agar or gelatin).

However, this method is not satisfactory because the high temperature cannot be applied because the substance falls again. Drying wet materials of this type at low temperatures is not economical because of the long residence time in the device.

[0028]

DISCLOSURE OF THE INVENTION It is therefore an object of the present invention to provide sheet-form, individually formulated, dosage forms which rapidly degrade in water. It is another object of the invention to provide a process for the production of such dosage forms.

This method requires only a very small amount of water in order to have sufficient fluidity for the preparation by the knife or roll application process, but nevertheless a delicate carrier is required. Brings a film of uniform thickness on top and has good adhesion to the carrier in the dry state,
At the same time, still easy separation from the carrier during subsequent processing and before administration, eg separation by punching, is possible.

According to the present invention, the object is to enable one dose for oral administration or uptake of medicines, confectionery and other foods, cosmetics and the like in the form of a sheet,
20-60% by weight of at least one film former, 2-40% by weight of at least one gel former,
0.1-35% by weight of at least one active substance, 4
Achieved by unsupported dosage forms consisting of less than 0% by weight of at least one inert filler agent with the substance applied on a carrier or of the substances with the abovementioned components.

The purpose of providing a process for the production of this type of product is to prepare an intimate mixture of the abovementioned components, optionally by adding less than 30% by weight of polar solvent, and to obtain a uniform, spreadable product. Alternatively, it is accomplished by processing into an extrudable material.

In this case, the weight percent display is 4
It relates to the mass of the basic components without solvent.

Surprisingly, the formulation according to the invention can be made spreadable by adding a small amount of polar solvent. Contrary to previously known formulations, they produce uniform films at low temperature on already delicate carriers.

In the dry state, the products can be separated by punching, leaving the individual formulations on the common carrier already used for spreading and drying.

The dosage form according to the invention decomposes completely in the mouth within 10 minutes, producing only those components which are acceptable under current German law for food products.

Suitable fillers include alkaline earth metal carbonates, phosphates, silicates, sulphates and oxides, zinc oxide, silica, cellulose and its derivatives, talc or titanium dioxide.

However, slightly soluble sugars or their derivatives, such as lactose, or starch derivatives, such as cyclodextrins, are also present in the product in virtually dissolved form, so that they are compatible with the mechanical properties of the filler. If you do, you can use it.

The term film-forming agent includes sugar, sugar alcohol, and derivatives thereof such as cane sugar, sorbitol, mannitol, pentitol, glucose, fructose, lactose, galactose, low molecular weight organic acids such as succinic acid, maleic acid or It should include adipic acid, polyethylene glycol, or mixtures of these substances, such as honey.

The third major component according to the invention is a water-swellable gel-forming agent, which is generally a polymeric carbohydrate such as starch and its derivatives, agar, alginic acid, arabinogalactan.
an) galactomannan
n), cellulose and its derivatives, carrageen (ca)
rageen), dextran,
It is based on tragacanth, and numerous gums of botanical origin.

However, synthetic polymers which are soluble or swellable in water can also be used according to the invention, examples of which include polyvinylpyrrolidine, polyvinyl alcohol, polyacrylic acid or polyacrylamide.
Polypeptides such as gelatin, albumin, collagen, or egg white may also be used.

Ingredients that act as fillers, film formers and gel formers are the major constituents that give the product with the desired properties, but they are individual when the amount of formulation is determined and when they are processed together. It only occurs according to the characteristics of. In this case, fillers or active substances which act as fillers can be used.

While the above-described advantageous properties are maintained when the mixing ratio is within the proper range, it is the film former 2
0 to 60% by weight, gel former 2 to 40% by weight, active substance 0.1 to 35% by weight, filler less than 40% by weight.

The treatment can be performed by a method known to those skilled in the art.

In general, the starting materials are premixed in the dry state and then converted to a spreadable concentration of the material with the addition of polar solvents in an amount not exceeding 30% by weight.

It is useful to use a homogenizer to obtain a more uniform mixture, or to use a vacuum to remove air bubbles.

Dispersion and grinding devices (ball mills) with floating grinding members are useful here.

Heating accelerates the dispersion process to form the desired physicochemical properties of the original product, but this is a matter of the particular nature of the gel and film former.

The addition of water would be unnecessary if the film-forming material melts.

A superficially uniform spreadable or extrudable material is obtained.

Shaping is generally done by a spread / knife coating or extrusion process, in this latter case the material passes through a gap of a given diameter, for example a slot die of an extruder, to give it a contour. When the solvent still remains, it is at least partially removed by suitable drying equipment known to those skilled in the art.

The product is preferably dried, even after drying, on a carrier to which it is adhered by adhesion.

When the initial product is not thick enough due to process technology, two or more layers may be laminated on top of them by pressing and, if necessary, heating.

The division into individual formulations is carried out by cutting, punching, embossing or similar processes to form areas of defined or separable size.
If the drying is carried out on a carrier, the dosage form will remain after said separating step until it is dispensed on this carrier, which makes its removal very easy.

[0054]

The present invention will be described in more detail by the following examples.

Example 1 75 g of acetylated starch 62 g of honey 55 g of calcium dihydrate sulfate 5 g of citric acid 50 g of water are mixed in a closed stirrer and heated to 50.degree. The mixture is homogenized by stirring for 2 hours and then cooled to room temperature. Stirring is continued under vacuum for half an hour and evaporated water is added again.

Add 2 ml peppermint oil and stir in for 5 minutes. The homogenized material is spread on a siliconized paper with a gap width of 500 μm by means of an applicator and dried for 15 minutes at 80 ° C.

The cutting lines that define the later shape are formed in the dried material by a suitable cutting machine without damaging the paper carrier.

Residual material between the removed individual dosed dosage forms is removed in a one-step step by mechanical drawing.

In order to prevent the dosage form from drying out, a composite packaging material made of paper / aluminum / ethylene vinyl-acetate which is virtually impermeable to water vapor through 12 groups each placed on a common paper carrier strip. To be contained within.

Use, flavor carrier (sweetener) Example 2 100 g of polyethylene glycol (molecular weight about 1500)
g / mol) 8 g of carboxyvinyl copolymer can be heated at 80 ° C Double Z kneader
Mix until uniform (within 2 hours).

70 g of lactose are added and kneaded into the basic substance in 30 minutes. Lower the temperature to 50 ° C.

8 g of glibencuramide
Clamid) is added and the mixture is kneaded for a further 30 minutes. Charge the hot mixture into a plunger extruder (working volume about 150 ml) preheated to 50 ° C.

About 10 g through a 10 × 1 mm sheet die
Immediately start extruding at a transfer rate of / min and cool until solidified on a cooled clean work surface.

The finished extrudate is divided by a knife into 10 mm pieces. An orally administrable form of the drug having a weight of about 80 mg and having about 3 mg of active substance is obtained, which decomposes in the mouth.

Example 3 25 g of acetylated starch 20 g of sorbitol 30 g of calcium carbonate 1 g of titanium dioxide 22 g of water 8 g of glycerol are mixed in a closed stirrer and heated to 50.degree. The mixture is stirred for 2 hours to homogenize and then cooled to room temperature.

Stirring is continued for half an hour under vacuum, compensating for the evaporated water. Add 0.5 ml peppermint oil and add 5
Stir over a period of minutes and incorporate evenly.

The mixture is spread on siliconized paper by means of a coater with a gap width of 500 μm and dried at 80 ° C. for 10 minutes.

The subsequent shape-defining cuts are made in the dried material using suitable cutting equipment without damaging the paper carrier. The material remaining between the individual dosage forms obtained is removed by mechanical stripping.

On a paper carrier, each dosage form is individually encapsulated in a substantially water vapor impermeable paper / aluminum / ethylene vinyl acetate composite packaging material.

Uses Instant toothpaste Example 4 600 g of acetylated starch 440 g of calcium dihydrate sulfate 40 g of citric acid Weighed into a ceramic ball mill containing 10 mill members (diameter about 4 cm) and closed. Premix in the mill in the dry state for 1 hour at 10 rpm. Suspension described below: 20 g of titanium dioxide are added to 550 g of water and the mixture is stirred in the same state for 1 hour.

Add 500 g of honey. Equalize 10
Continue at rpm for 2 hours. Finally add 16 ml peppermint oil and continue spinning for 18 hours. Subsequent processing of the finished material is carried out as described in Example 1.

It should be apparent that the description and examples are illustrative and not limiting of the invention, and that one of ordinary skill in the art will be aware of other examples within the spirit and scope of the invention. is there.

─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] June 23, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] Full text

[Correction method] Change

[Correction content]

[Document name] Statement

Title: Rapidly degrading sheet-like dosage form and process for its production

[Claims]

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a sheet-shaped dosage form for oral administration or uptake of pharmaceuticals, confectionery, other foods, cosmetics and the like, and a method for producing the same.

[0002]

BACKGROUND OF THE INVENTION Pharmaceutical dosage forms of medicinal products, confectionery and other foodstuffs, as well as cosmetics to be applied to the oral area or in principle to be orally administered, are in principle free to administer by the person who administers or by the manufacturer. It is possible to be already pre-divided into dispensing units.

Such dispensed forms are especially common in the pharmaceutical industry in the form of tablets, capsules, coated tablets, pills, lozenges and the like.

Compared to drop solutions, ointments or creams which have to be dispensed by the user, in these cases an unintended undesired dispensing by the user is prevented.

From an application point of view, tablets have a certain minimum size (diameter 5 to 6 mm) and a certain minimum weight (about 10) to facilitate the handling of these dosage forms.
Must be 0 to 200 mg). Therefore, especially effective drugs are about 99% of the weight of tablets.
May contain inactive ingredients of.

[0006] Foods, especially confectioneries, are also often found on the market in individually formulated forms (candies, sweetener tablets, peppermint tablets, etc.). Here again-for example in the case of candy-there is the desire to achieve the desired taste by using a small amount of auxiliary agent (usually sugar).

For this reason, numerous technical proposals have recently been made, which aim to ensure the safe handling of these substances as well as the reduction of the amount of inactive ingredients in the product. .

Proposals of particular interest in this context are, for example, DE 3534983, DE 2746414,
BE637363, DE2432925, or D
The production of a sheet-shaped active substance carrier as described in the respective publications of E3630303.

According to known production methods, paper-like carriers of this type are first produced without active substance and then spray-coated with an active substance-containing solution (eg GB 1061).
557), and coating / printing with a high-concentration active substance-containing layer (eg, EP0219762).

However, conventional spraying or molding (eg JP 69026674) and drying, followed by complete or incomplete dissolution of the active or inactive substance in water or other solvent (DE 244986).
No. 5) can be expected to be the method of choice of those skilled in the art.

Extrusion under heating has also been proposed {Reserch Disc Closure, 1986, No. 26
March, March, 145 to 146 (No. 26341)}.

Film-like formations promise the possibility of enormous variation in the separation of individual doses. These can be envisioned as having the shape of a stamp sheet that can be partially withdrawn from the complete composite in a very short time before use (eg BE637363, EP.
No. 0219762).

Individual doses of different size can also be promised from the tape-shaped dosage form, for example separated by perforation (eg DE 27464).
14 publication). Especially when using non-edible carriers (DE 3630603), it is absolutely necessary for complete separation into the individual parts, which requires a more hygienic, easy and safe separation.

Although a number of flat-shaped dosing regimens and methods are known to the person skilled in the art, the physics of pharmaceutical carriers such as, for example, the selection of adjuvants, and of sheet carriers of this type. There are still considerable deficiencies in the concept of chemical microstructure. Numerous purposes and aims must be taken into account.

Rapid disintegration is required for a large number of pharmaceuticals to allow rapid swallowing of the pharmaceutical dosage unit, while in other circumstances the pharmaceuticals may be temporarily edible. Adhesion to mucous membranes is required, and in other cases, for example short-acting pharmaceuticals, degradation with considerable delay is desired. In the case of confectionery, intermediate maintenance of, for example, flavor in the mouth is usually preferred.

The cosmetic film dentifrice should be flexible and disintegrate as soon as possible.

In general, the dosage form in sheet form must not be too brittle so that it can be safely transferred from its part to the destination. If a carrier is used, both materials must be properly fitted and adherent to each other for two reasons, one of which is the separation of the medication, for example by partial punching of the isolation insert and peel-off. Must be ensured during manufacture, and secondly, adhesion to the carrier must be effective during storage.

When drying is required during manufacture, it should be possible to make a spreadable formulation with as little solvent (preferably water) as possible and use as little energy as possible during the drying process. is there.

The pharmaceutical compositions known to date do not meet these requirements. The basic principle of tablet technology is described in DE 2746414 in the context of film tapes, which involves the use of thermoplastic binders or other auxiliaries as desired, chemical cross-linking, Or the addition of hydrophobic substances to delay degradation,
The combination of a few layers and the use of microencapsulated active substances.

Known tablet disintegrants use therein a disintegration aid for the film. According to the findings of the inventors themselves, these proposals cannot be applied to new medicinal products.

The conventional decomposing agent is a porous, mechanically stable environment formed by the adhesive force between particles, assuming that the decomposition is caused by swelling due to addition of water or accumulated elastic deformation energy. Need a situation.

However, these prerequisites do not always exist in the case of sheet-like dosage forms which are always slightly flexible and have low porosity. The swellable particles may delay the degradation of the film by removing water.

According to DE 2432925, the formulation contains a water-soluble cellulose ether, a separating agent and, if desired, a filler. Originally, however, most water-soluble polymers always required the addition of large amounts of water to make the material of sufficiently low viscosity for spreads or moulds, but this structure requires high drying costs during manufacture. Will be included.

In addition to this, the adhesive bond to the base is affected by the extreme shrinkage of this type of material.

When a sheet-form dosage form is made by spreading a water-based substance onto a dehesive paper or film, the liquid easily runs off the support due to surface tension. Or at least form areas of different film thickness. Even if the viscosity is increased by adding a cellulose derivative or the like, it becomes more difficult to spread through a minute gap.

According to another source (eg DE 3534981, DE 3630603), viscosity-forming substances are therefore recommended, although these lead to low viscosity solutions by heat (in the coating machine), but Immediately after that, a gel-like stable film is formed by cooling,
Dry completely in air (eg agar or gelatin).

However, this method is not satisfactory because the high temperature cannot be applied because the substance falls again. Drying such highly hydrated materials at low temperatures is not economical because of the long residence time in the equipment.

[0028]

DISCLOSURE OF THE INVENTION It is therefore an object of the present invention to provide sheet-form, individually formulated, dosage forms which rapidly degrade in water. It is another object of the invention to provide a process for the production of such dosage forms.

This method requires only a very small amount of water in order to have sufficient fluidity for preparation by the knife or roll application process, but nevertheless a delicate carrier Brings a film of uniform thickness on top and has good adhesion to the carrier in the dry state,
At the same time, still easy separation from the carrier during subsequent processing and before administration, eg separation by punching, is possible.

According to the present invention, the object is to enable one dose for oral administration or uptake of medicines, confectionery and other foods, cosmetics and the like in the form of a sheet,
20-60% by weight of at least one film former, 2-40% by weight of at least one gel former,
0.1-35% by weight of at least one active substance, 4
Achieved by unsupported dosage forms consisting of less than 0% by weight of at least one inert filler agent with the substance applied on a carrier or of the substances with the abovementioned components.

The purpose of providing a process for the production of this type of product is to prepare an intimate mixture of the abovementioned components, optionally by adding less than 30% by weight of polar solvent, and to obtain a uniform, spreadable product. Alternatively, it is accomplished by processing into an extrudable material.

In this case, the weight percent display is 4
It relates to the mass of the basic components without solvent.

Surprisingly, the formulation according to the invention can be made spreadable by adding a small amount of polar solvent. Contrary to previously known formulations, they produce uniform films at low temperature on already delicate carriers.

In the dry state, the products can be separated by punching, leaving the individual formulations on the common carrier already used for spreading and drying.

The dosage form according to the invention decomposes completely in the mouth within 10 minutes, producing only those components which are acceptable under current German law for food products.

Suitable fillers include alkaline earth metal carbonates, phosphates, silicates, sulphates and oxides, zinc oxide, silica, cellulose and its derivatives, talc or titanium dioxide.

However, slightly soluble sugars or their derivatives, such as lactose, or starch derivatives, such as cyclodextrins, are also present in the product in virtually dissolved form, so that they are compatible with the mechanical properties of the filler. If you do, you can use it.

The term film formers include sugars, sugar alcohols, and their derivatives such as cane sugar, sorbitol, mannitol, xitol, glucose, fructose, lactose, galactose, low molecular weight organic acids such as succinic acid, maleic acid or adipine. It should include acids, polyethylene glycols, or mixtures of these substances, such as honey.

The third major component according to the invention is a water-swellable gel-forming agent, which is generally a polymeric carbohydrate such as starch and its derivatives, agar, alginic acid, arabinogalactan.
an) galactomannan
n), cellulose and its derivatives, carrageen (ca)
rageen), dextran,
It is based on tragacanth, and numerous gums of botanical origin.

However, synthetic polymers which are soluble or swellable in water can also be used according to the invention, examples of which include polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid or polyacrylamide.
Polypeptides such as gelatin, albumin, collagen, or egg white may also be used.

Ingredients that act as fillers, film formers and gel formers are the major constituents that give the product with the desired properties, but they are individual when the amount of formulation is determined and when they are processed together. It only occurs according to the characteristics of. In this case, fillers or active substances which act as fillers can be used.

While the above-described advantageous properties are maintained when the mixing ratio is within the proper range, it is the film former 2
0 to 60% by weight, gel former 2 to 40% by weight, active substance 0.1 to 35% by weight, filler less than 40% by weight.

The treatment can be performed by a method known to those skilled in the art.

In general, the starting materials are premixed in the dry state and then converted to a spreadable concentration of the material with the addition of polar solvents in an amount not exceeding 30% by weight.

It is useful to use a homogenizer to obtain a more uniform mixture, or to use a vacuum to remove air bubbles.

Dispersion and grinding devices (ball mills) with floating grinding members are useful here.

Heating accelerates the dispersion process to form the desired physicochemical properties of the original product, but this is a matter of the particular nature of the gel and film former.

The addition of water would be unnecessary if the film-forming material melts.

A superficially uniform spreadable or extrudable material is obtained.

Shaping is generally done by a spread / knife coating or extrusion process, in this latter case the material passes through a gap of a given diameter, for example a slot die of an extruder, to give it a contour. When the solvent still remains, it is at least partially removed by suitable drying equipment known to those skilled in the art.

The product is preferably dried, even after drying, on a carrier to which it is adhered by adhesion.

When the original product is not thick enough due to process technology, two or more layers may be laminated on top of them by pressing and, if necessary, heating.

The division into individual formulations is carried out by cutting, punching, embossing or similar processes to form areas of defined or separable size.
If the drying is carried out on a carrier, the dosage form will remain after said separating step until it is dispensed on this carrier, which makes its removal very easy.

[0054]

The present invention will be described in more detail by the following examples.

Example 1 75 g of acetylated starch 62 g of honey 55 g of calcium sulfate dihydrate 5 g of citric acid 50 g of water are mixed in a closed stirrer and heated to 50.degree. The mixture is homogenized by stirring for 2 hours and then cooled to room temperature. Stirring is continued under vacuum for half an hour and evaporated water is added again.

Add 2 ml peppermint oil and stir in for 5 minutes. The homogenized material is spread on a siliconized paper with a gap width of 500 μm by means of an applicator and dried for 15 minutes at 80 ° C.

The cutting lines that define the later shape are formed in the dried material by a suitable cutting machine without damaging the paper carrier.

Residual material between the removed individual dosed dosage forms is removed in a one-step step by mechanical drawing.

In order to prevent the dosage form from drying out, a composite packaging material made of paper / aluminum / ethylene vinyl-acetate which is virtually impermeable to water vapor through 12 groups each placed on a common paper carrier strip. To be contained within.

Use, flavor carrier (sweetener) Example 2 100 g of polyethylene glycol (molecular weight about 1500)
g / mol) 8 g of carboxyvinyl copolymer can be heated at 80 ° C Double Z kneader
Mix until uniform (within 2 hours).

70 g of lactose are added and kneaded into the basic substance in 30 minutes. Lower the temperature to 50 ° C.

8 g of glibencuramide
Clamid) is added and the mixture is kneaded for a further 30 minutes. Charge the hot mixture into a plunger extruder (working volume about 150 ml) preheated to 50 ° C.

About 10 g through a 10 × 1 mm sheet die
Immediately start extruding at a transfer rate of / min and cool until solidified on a cooled clean work surface.

The finished extrudate is divided by a knife into 10 mm pieces. An orally administrable form of the drug having a weight of about 80 mg and having about 3 mg of active substance is obtained, which decomposes in the mouth.

Example 3 25 g of acetylated starch 20 g of sorbitol 30 g of calcium carbonate 1 g of titanium dioxide 22 g of water 8 g of glycerine are mixed in a closed stirrer and heated to 50.degree. The mixture is stirred for 2 hours to homogenize and then cooled to room temperature.

Stirring is continued for half an hour under vacuum, compensating for the evaporated water. Add 0.5 ml peppermint oil and add 5
Stir over a period of minutes and incorporate evenly.

The mixture is spread on siliconized paper by means of a coater with a gap width of 500 μm and dried at 80 ° C. for 10 minutes.

The subsequent shape-defining cuts are made in the dried material using suitable cutting equipment without damaging the paper carrier. The material remaining between the individual dosage forms obtained is removed by mechanical stripping.

On a paper carrier, each dosage form is individually encapsulated in a substantially water vapor impermeable paper / aluminum / ethylene vinyl acetate composite packaging material.

Uses Instant toothpaste Example 4 600 g of acetylated starch 440 g of calcium sulfate dihydrate 40 g of citric acid Weighed into a ceramic ball mill containing 10 mill members (diameter about 4 cm). Premix dry for 1 hour at 10 rpm in a closed mill. Suspension described below: 20 g of titanium dioxide are added to 550 g of water and the mixture is stirred in the same state for 1 hour.

Add 500 g of honey. Equalize 10
Continue at rpm for 2 hours. Finally add 16 ml peppermint oil and continue spinning for 18 hours. Subsequent processing of the finished material is carried out as described in Example 1.

It should be apparent that the description and examples are illustrative and not limiting of the invention, and that one of ordinary skill in the art will be aware of other examples within the spirit and scope of the invention. is there.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication location C08L 101/00 LSY // A61K 7/16 (72) Inventor Stefan Hungerbach, Federal Republic of Germany, Day 5401 Nörters Haocen, Haoptstraße 42

Claims (17)

[Claims] 1. 20 to 60% by weight of at least one film former, 2 to 40% by weight of at least one gel former and 0.1 to 35% by weight of at least one active substance. And less than 40% by weight of at least one inert filler, which is applied on a carrier or is rapidly decomposed in water without support made up of the substances of the abovementioned components. Individually-administered dosage forms in the form of sheets of orally administered or incorporated medications, confectionery, other foodstuffs, cosmetics, and the like. 2. The dosage form according to claim 1, wherein an appropriate amount of polar solvent is added to render the substance fluid, and the solvent is not removed during drying. 3. The thickness of the layer of material is 0.003-4 mm,
The dosage form according to claim 1 or 2, which is preferably 20 to 400 μm, in particular 70 to 150 μm. 4. The dosage form according to claim 1, wherein the substance is applied to a release paper or release film. 5. A dosage form according to claim 1 or 2, wherein the film-forming agent consists essentially of a mixture of monomeric or oligomeric sugars or sugar derivatives of sugar alcohols or polyethylene glycols. 6. The gel forming agent is a polymeric carbohydrate or its derivative, gelatin, carboxyvinyl copolymer,
4. The dosage form according to any one of claims 1 to 3, which is polyvinyl alcohol or a mixture of such substances. 7. A dosage form according to any one of claims 1 to 4, wherein the active substance is a pharmaceutically active substance. 8. The filler is calcium carbonate, calcium sulfate, calcium phosphate, carbohydrates in crystalline or partially crystalline form, talc, titanium dioxide, zinc oxide, magnesium stearate, or mixtures of these substances. 6. The dosage form according to any one of 1 to 5. 9. The dosage form according to claim 1, wherein there are at least two active substance-containing layers. 10. A dosage form according to any one of claims 1 to 9 having individually dosed portions. 11. 20-60% by weight film former, 2-40% by weight gel former, maximum 40% by weight.
A process for making a rapidly disintegrating sheet-like dosage form, which comprises intimately mixing the base material, which comprises an inert filler of, and treating it to form a uniform spreadable or extrudable material. 12. A polar solvent is added to the mixture of film formers, gel formers, active substances and fillers in an amount not exceeding 30% by weight, based on the composition, wherein the polar solvent is a 12. The method for producing a rapidly degrading sheet-like dosage form according to claim 11, which is at least partly removed in a drying step performed after the treatment of the layer by the action of and / or the action of vacuum. 13. Rapidly disintegrating sheet dosage according to any one of claims 1 to 10, wherein the spreadable substance is prepared by using a film former which dissolves at processing temperature without the addition of a solvent. A method of manufacturing a formed product. 14. The method for producing a rapidly degrading sheet-like dosage form according to claim 11, wherein a homogenizer is used for producing a uniform, spreadable substance. 15. The method for producing a rapidly degrading sheet-like dosage form according to claim 11, wherein the mixing is carried out in a ball mill. 16. A method for producing a rapidly degrading sheet-like dosage form according to claim 11, wherein the mixing is carried out under vacuum. 17. The method according to any one of claims 1 to 10, which is used as a pharmaceutical therapeutic agent for human or animal diseases, as a cosmetic agent, as an administration agent for aroma or flavor, or as an instant preparation for plant tea. Use of the composition according to claim 1 and / or the product obtained by the method according to any one of claims 11 to 16.